Eleven undescribed sesquiterpenoids with multiple skeleton types and cytotoxicity from the South China Sea soft coral Lemnalia sp

Area of Science:

• Marine natural products chemistry
• Drug discovery
• Organic chemistry

Background:

• Marine organisms, particularly corals, are a rich source of novel bioactive compounds.
• Soft corals are known for producing diverse and complex secondary metabolites.
• Sesquiterpenoids represent a significant class of natural products with potential therapeutic value.

Purpose of the Study:

• To isolate and characterize new sesquiterpenoids from the soft coral Lemnalia sp.
• To elucidate the structures and absolute configurations of these novel compounds.
• To evaluate the bioactivity of the isolated compounds.

Main Methods:

• Isolation and purification of compounds using chromatographic techniques.
• Structure elucidation via extensive spectroscopic data analysis (NMR, MS).
• Determination of absolute configurations using single crystal X-ray diffraction and quantum chemical calculations (TDDFT-ECD).

Main Results:

• Eleven new sesquiterpenoids (lemnalinoids A-K) and one known sesquiterpenoid were isolated.
• Compounds 1-3 possess unusual spironolactone structures; compound 1 is a rare brominated sesquiterpenoid.
• Compounds 4-6 are rare sesquiterpenoid alkaloids; compound 7 features a unique 6/5/6 tricyclic system; compounds 8-11 are novel nardosinane/nornardosinane derivatives.
• Compound 2 demonstrated cytotoxicity against NCI-H446 lung cancer cell lines (IC50 = 19.32 μM).

Conclusions:

• The study expands the chemical diversity of marine sesquiterpenoids.
• Compound 2 shows promising cytotoxic activity, warranting further investigation for cancer therapy.
• Molecular docking suggests potential mechanisms involving inhibition of VEGFR2, CD56, and PARP proteins.